Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillan...Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.展开更多
Background: SARS-CoV-2 has circulated worldwide with dramatic consequences. In Chad, we have no data reported of variants. The aim of this study was to identify the SARS-CoV-2 variants that circulated during the epide...Background: SARS-CoV-2 has circulated worldwide with dramatic consequences. In Chad, we have no data reported of variants. The aim of this study was to identify the SARS-CoV-2 variants that circulated during the epidemic from 2020 to 2021. Methods: This is a cross-sectional, descriptive study carried out between 2020 and 2021. Samples from patients with suspected COVID-19 were tested in five laboratories in N’Djamena. One hundred quality samples of the positives were sequenced in Kinshasa using Oxford nanopore technologies minion and the Protocol Midnight SARS-CoV2. Data were processed using Excel version 16 software. Results: Of the 100 samples sequenced, 77 (77%) produced sequences, 23 (23%) did not. The genomic profiles were wild-type Wuhan and minor mutations (19A, 19B (A), 20A (B.1, B.2), 20B (AV.1), 20D (B.1.1.1 /C.36), 20C), variant of concern Alpha (20I), variant of concern Delta (21A/J), variant of interest Eta (21D), variant of concern Omicron (21K) and unclassified variant under surveillance (B.1.640). Of these variants, the maximums were detected in patients aged 26 - 35 with 30.26% and 25.26% in 36 - 45. However, 24.67% were in travelers and 75.32% in residents, 35.06% in those vaccinated against COVID-19 and 62.33% in non-vaccinates. The estimated case-fatality rate was 2.44% (107/4374). Conclusion: This work has provided preliminary data on COVID-19 and SARS-CoV-2 variants circulating during the 2020-2021 epidemics in Chad.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.展开更多
Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,result...Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.展开更多
Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve a...Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)has been shown to increase the risk of stroke.However,the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack(TIA),as w...BACKGROUND Coronavirus disease 2019(COVID-19)has been shown to increase the risk of stroke.However,the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack(TIA),as well as its impact on mor-tality,are not established.AIM To evaluate the impact of COVID-19 on in-hospital mortality,length of stay,and healthcare costs in patients with recurrent strokes.METHODS We identified admissions of recurrent stroke(current acute ischemic stroke admissions with at least one prior TIA or stroke)in patients with and without COVID-19 using ICD-10-CM codes using the National Inpatient Sample(2020).We analyzed the impact of COVID-19 on mortality following recurrent stroke admissions by subgroups.RESULTS Of 97455 admissions with recurrent stroke,2140(2.2%)belonged to the COVID-19-positive group.The COVID-19-positive group had a higher prevalence of diabetes and chronic kidney disease vs the COVID-19 negative group(P<0.001).Among the subgroups,patients aged>65 years,patients aged 45–64 years,Asians,Hispanics,whites,and blacks in the COVID-19 positive group had higher rates of all-cause mortality than the COVID-19 negative group(P<0.01).Higher odds of in-hospital mortality were seen in the group aged 45-64(OR:8.40,95%CI:4.18-16.91)vs the group aged>65(OR:7.04,95%CI:5.24-9.44),males(OR:7.82,95%CI:5.38-11.35)compared to females(OR:6.15,95%CI:4.12-9.18),and in Hispanics(OR:15.47,95%CI:7.61-31.44)and Asians/Pacific Islanders(OR:14.93,95%CI:7.22-30.87)compared to blacks(OR:5.73,95%CI:3.08-10.68),and whites(OR:5.54,95%CI:3.79-8.09).CONCLUSION The study highlights the increased risk of all-cause in-hospital mortality in recurrent stroke patients with COVID-19,with a more pronounced increase in middle-aged patients,males,Hispanics,or Asians.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and vir...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.展开更多
Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,t...Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5%to 96.8%worldwide.The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West.Multifactorial mechanisms are implicated in COVID-19-induced liver injury.Among them,hypercytokinemia with“bystander hepatitis”,cytokine storm syndrome with subsequent oxidative stress and endotheliopathy,hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury.Liver hypoxia may also contribute under specific conditions,while direct hepatocyte injury is an emerging mechanism.Except for initially observed severe acute respiratory distress syndrome corona virus-2(SARS-CoV-2)tropism for cholangiocytes,more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy(EM).The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA,S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization.New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery,suggesting a post-COVID-19 persistent live injury.展开更多
The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodi...The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.展开更多
BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemi...BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.展开更多
Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United State...Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.展开更多
Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is ai...Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is aimed to investigate whether the increasing otitis media cases recently is correlated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the COVID-19-related otitis media is commonly existed. Thirty-two patients with otitis media were enrolled Blood cell analysis, C-reactive protein, interleukin-6 test bacterial and fungal cultures were tested. Nine patients were identified with positive SARS-CoV-2 RNA in middle ear discharge. All the subjects had the common symptoms of stuffy ear, hearing loss, and echoacousia. No positive results were found in cultures for bacterial and fungus of middle ear discharge. The levels of C-reactive protein (CRP) were significantly up-regulated in positive cases (P = 0.0335). The levels of proinflammatory cytokine interleukin-6 (IL-6) were higher in positive cases. There were no significant differences of age, gender and prothrombin time (PT) between positive and negative cases. Nasal sprays, ciliary stimulants, and prophylactic antibiotics or low-dose steroid treatments were sequentially used in the otitis media patients caused by SARS-CoV-2 infection. All the patients had improvements of typical symptoms within two to four weeks during the following-up. Thus, SARS-CoV-2 infection caused COVID-19 related otitis media is commonly existed, and the prognosis is good after treatments.展开更多
Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the...Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.展开更多
Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome corona...Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.展开更多
The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole...The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.展开更多
Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute resp...Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.展开更多
文摘Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
文摘Background: SARS-CoV-2 has circulated worldwide with dramatic consequences. In Chad, we have no data reported of variants. The aim of this study was to identify the SARS-CoV-2 variants that circulated during the epidemic from 2020 to 2021. Methods: This is a cross-sectional, descriptive study carried out between 2020 and 2021. Samples from patients with suspected COVID-19 were tested in five laboratories in N’Djamena. One hundred quality samples of the positives were sequenced in Kinshasa using Oxford nanopore technologies minion and the Protocol Midnight SARS-CoV2. Data were processed using Excel version 16 software. Results: Of the 100 samples sequenced, 77 (77%) produced sequences, 23 (23%) did not. The genomic profiles were wild-type Wuhan and minor mutations (19A, 19B (A), 20A (B.1, B.2), 20B (AV.1), 20D (B.1.1.1 /C.36), 20C), variant of concern Alpha (20I), variant of concern Delta (21A/J), variant of interest Eta (21D), variant of concern Omicron (21K) and unclassified variant under surveillance (B.1.640). Of these variants, the maximums were detected in patients aged 26 - 35 with 30.26% and 25.26% in 36 - 45. However, 24.67% were in travelers and 75.32% in residents, 35.06% in those vaccinated against COVID-19 and 62.33% in non-vaccinates. The estimated case-fatality rate was 2.44% (107/4374). Conclusion: This work has provided preliminary data on COVID-19 and SARS-CoV-2 variants circulating during the 2020-2021 epidemics in Chad.
基金Supported by University of Edinburgh Hepatology Laboratory Internal Fundingthe Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.
文摘Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.
文摘Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)has been shown to increase the risk of stroke.However,the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack(TIA),as well as its impact on mor-tality,are not established.AIM To evaluate the impact of COVID-19 on in-hospital mortality,length of stay,and healthcare costs in patients with recurrent strokes.METHODS We identified admissions of recurrent stroke(current acute ischemic stroke admissions with at least one prior TIA or stroke)in patients with and without COVID-19 using ICD-10-CM codes using the National Inpatient Sample(2020).We analyzed the impact of COVID-19 on mortality following recurrent stroke admissions by subgroups.RESULTS Of 97455 admissions with recurrent stroke,2140(2.2%)belonged to the COVID-19-positive group.The COVID-19-positive group had a higher prevalence of diabetes and chronic kidney disease vs the COVID-19 negative group(P<0.001).Among the subgroups,patients aged>65 years,patients aged 45–64 years,Asians,Hispanics,whites,and blacks in the COVID-19 positive group had higher rates of all-cause mortality than the COVID-19 negative group(P<0.01).Higher odds of in-hospital mortality were seen in the group aged 45-64(OR:8.40,95%CI:4.18-16.91)vs the group aged>65(OR:7.04,95%CI:5.24-9.44),males(OR:7.82,95%CI:5.38-11.35)compared to females(OR:6.15,95%CI:4.12-9.18),and in Hispanics(OR:15.47,95%CI:7.61-31.44)and Asians/Pacific Islanders(OR:14.93,95%CI:7.22-30.87)compared to blacks(OR:5.73,95%CI:3.08-10.68),and whites(OR:5.54,95%CI:3.79-8.09).CONCLUSION The study highlights the increased risk of all-cause in-hospital mortality in recurrent stroke patients with COVID-19,with a more pronounced increase in middle-aged patients,males,Hispanics,or Asians.
基金supported by the Innovation and Entrepreneurship Training Program for College Students in Henan University(20221022009)the Key Scientific Research Project of Henan Province(22A310012)+1 种基金supporting program for Central Plain Young Top Talents(ZYQR201912176)the program from Academy for Advanced Interdisciplinary Studies of Henan University(Y21008L).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.
文摘Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5%to 96.8%worldwide.The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West.Multifactorial mechanisms are implicated in COVID-19-induced liver injury.Among them,hypercytokinemia with“bystander hepatitis”,cytokine storm syndrome with subsequent oxidative stress and endotheliopathy,hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury.Liver hypoxia may also contribute under specific conditions,while direct hepatocyte injury is an emerging mechanism.Except for initially observed severe acute respiratory distress syndrome corona virus-2(SARS-CoV-2)tropism for cholangiocytes,more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy(EM).The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA,S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization.New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery,suggesting a post-COVID-19 persistent live injury.
文摘The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.
文摘BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.
文摘Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.
文摘Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is aimed to investigate whether the increasing otitis media cases recently is correlated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the COVID-19-related otitis media is commonly existed. Thirty-two patients with otitis media were enrolled Blood cell analysis, C-reactive protein, interleukin-6 test bacterial and fungal cultures were tested. Nine patients were identified with positive SARS-CoV-2 RNA in middle ear discharge. All the subjects had the common symptoms of stuffy ear, hearing loss, and echoacousia. No positive results were found in cultures for bacterial and fungus of middle ear discharge. The levels of C-reactive protein (CRP) were significantly up-regulated in positive cases (P = 0.0335). The levels of proinflammatory cytokine interleukin-6 (IL-6) were higher in positive cases. There were no significant differences of age, gender and prothrombin time (PT) between positive and negative cases. Nasal sprays, ciliary stimulants, and prophylactic antibiotics or low-dose steroid treatments were sequentially used in the otitis media patients caused by SARS-CoV-2 infection. All the patients had improvements of typical symptoms within two to four weeks during the following-up. Thus, SARS-CoV-2 infection caused COVID-19 related otitis media is commonly existed, and the prognosis is good after treatments.
文摘Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.
基金the National Natural Science Foundation of China(82103662).
文摘Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.
基金National Key Research and Development Program of China(2022YFC2303700,2021YFC2301300)Yunnan Key Research and Development Program(202303AC100026)+2 种基金National Natural Science Foundation of China(82302002,82341069)Yunnan Fundamental Research Project(202201AS070047)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0490000)。
文摘The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.
文摘Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
